Functional status after lung transplantation in older adults in the post-allocation score era.

This manuscript describes the functional status trajectory of older (age 65 or older) and younger (age 18-64) adults after lung transplantation (LT). After the implementation of the lung allocation score (LAS) in 2005, older adults became the fastest growing subgroup of recipients. Yet the impact of LT on physical function, a main determinant of quality of life in older adults, is unknown. We conducted a retrospective cohort study using United Network for Organ Sharing data on 4805 adults who received a LT during 2005-2009. We divided them into older (≥65; n = 774) and younger (18-64; n = 4031) cohorts. Functional status was measured by Karnofsky performance score (KPS). Mixed models estimated the impact of age group on the rate of functional decline starting at 1 year posttransplantation. We controlled for KPS at transplantation, gender, race, diagnosis, LAS and LT type. Age group was not associated with different rates of decline in KPS over time. On average, recipients who were older, received a single LT, or had a low KPS at transplantation had worse functional status posttransplantation when compared to their counterparts, but rarely reached disability at 48 months. Overall, LT had a positive and durable effect on physical function for both older and younger recipients.

Inhibitor of calmodulin and cAMP phosphodiesterase activity in BB rats.

Diabetes mellitus in humans is associated with increased plasma and tissue levels of cAMP and decreased cAMP phosphodiesterase (PDE) activity. Calmodulin (CM) is a low-molecular-weight protein essential for activation of cAMP PDE. The inhibitor (INH) is a low-molecular-weight substance that inhibits the activity of CM in multiple systems, including PDE. Spontaneously diabetic BB rats (SDR) and their nondiabetic littermates (NDR) were used in this study. Holtzman rats were rendered diabetic by streptozocin (STZ). STZ-induced diabetic rats (STZ-DR) and BB rats were studied with and without the benefit of insulin therapy. Calmodulin was assayed both by bioassay and by specific radioimmunoassay. The inhibitor was bioassayed by its ability to inhibit CM-activated PDE. Results showed that both spontaneous and STZ-induced diabetes are associated with a decrease in activity of the low-Michaelis constant (Km) cAMP PDE in the liver (39%, SDR; 70% STZ-DR). Calmodulin activity was also decreased in the livers of both animals (13%, SDR; 68%, STZ-DR). Similar data were obtained for NDRs. The inhibitor, on the other hand, was increased in the livers of untreated SDRs and STZ-DRs (155%, SDR; 125%, STZ-DR). No change was noted for NDRs. All these changes were restored toward normal after treatment with insulin. These data suggest that in diabetes the defect in the cAMP PDE-CM-INH system is demonstrated in both an environmental model, as illustrated by STZ-DRs, and a genetic model, as shown by SDRs and NDRs. The inhibitor activity, however, is not changed significantly in NDRs. We speculate that the inhibitor activity plays a role in dictating whether the genetic NDR will or will not become clinically diabetic.

Physician attitudes about anticoagulation for nonvalvular atrial fibrillation in the elderly.

BACKGROUND: Our goal was to determine whether patient age affects a physician's reported likelihood of using anticoagulant therapy or the intensity of anticoagulant therapy for patients with nonvalvular atrial fibrillation. METHODS: We surveyed a nationwide sample of 1189 randomly selected office-based practitioners in three strata: primary care (geriatrics, internal medicine, family practice, and general practice), cardiology, and neurology. A vignette-based questionnaire was used to measure attitudes and beliefs regarding anticoagulation risks and effectiveness, barriers to anticoagulation in clinical practice, and likelihood of using anticoagulation and target intensity of anticoagulation at three patient ages (55, 65, and 75 years) for four clinical scenarios (chronic non-valvular atrial fibrillation with mild left atrial enlargement, intermittent or paroxysmal atrial fibrillation, recent-onset atrial fibrillation, and atrial fibrillation with recent [3 months] embolic stroke). RESULTS: The overall response rate was 38%. The mean likelihoods of using anticoagulation for the three ages were unequal (P < .0001) for each scenario. Most physicians were "very" or "somewhat" likely to use anticoagulant therapy for a 65-year-old with left atrial enlargement (71%), intermittent or paryoxysmal atrial fibrillation (68%), recent-onset atrial fibrillation (86%), or embolic stroke (96%). Fewer physicians were likely to use anticoagulant therapy for a 75-year-old with left atrial enlargement (63%), intermittent or paroxysmal atrial fibrillation (56%), recent-onset atrial fibrillation (80%), or embolic stroke (93%). Among physicians equally likely to use anticoagulation for 65- and 75-year-old patients, intensity of anticoagulant therapy (target international normalized ratio or prothrombin time ratio) was lower (P < .04) for the 75-year-old. CONCLUSION: Anticoagulant therapy may be less often and less intensively used for elderly patients with nonvalvular atrial fibrillation.

Staphylococcus aureus bacteremia among elderly vs younger adult patients: comparison of clinical features and mortality.

BACKGROUND: Previous studies give conflicting results regarding the effect of age on outcomes in Staphylococcus aureus bacteremia (SAB). These studies have been limited by retrospective design or small sample size. METHODS: We conducted a prospective cohort study of 385 patients with SAB aged 18 to 90 years. The setting was a large academic medical center. We observed patients from diagnosis of SAB to discharge or death. Discharged patients were contacted 12 weeks after their first positive culture findings. Data were collected on demographics, comorbid conditions, focus of infection, length of stay, and outcome. Primary outcomes were total mortality and death due to SAB. RESULTS: Comparisons were made between 145 patients, aged 66 to 90 years, and 240 patients, aged 18 to 60 years. Forty-three (29.7%) of the elderly patients and 36 (15%) of the younger patients died. Death directly attributable to SAB occurred in 21 (14.5%) older and 15 (6.3%) younger patients. After adjusting for confounding variables, older patients continued to have higher total mortality (odds ratio, 2.21; 95% confidence interval, 1.32-3.70), and higher mortality from SAB (odds ratio, 2.30; 95% confidence interval, 1.13-4.69). Infection with methicillin-resistant S aureus was associated with higher total mortality in the elderly (odds ratio, 2.59; 95% confidence interval, 1.23-5.43). CONCLUSIONS: Staphylococcus aureus bacteremia among the elderly is associated with high mortality. Both total mortality and mortality directly attributable to SAB are more than twice as likely in older patients. Infection with methicillin-resistant S aureus carries a worse prognosis than infection with methicillin-sensitive S aureus in the elderly.

A randomized trial of 3,4-diaminopyridine in Lambert-Eaton myasthenic syndrome.

OBJECTIVES: The authors report the results of a prospective, placebo-controlled, randomized study to evaluate the effectiveness of 3,4-diaminopyridine (DAP) in patients with Lambert-Eaton myasthenic syndrome (LEMS) and to determine the acute and long-term side effects of DAP. METHODS: Twenty-six patients with LEMS completed a two-arm parallel treatment protocol in which DAP, 20 mg three times daily, or placebo was given blindly for 6 days, and a quantitative examination of muscle strength (the quantitative myasthenia gravis [QMG] score) was used as the primary measure of efficacy. After the blinded study, patients were given open-label DAP and monitored for side effects as long as there was symptomatic improvement. RESULTS: Twelve patients took DAP, and 14 took placebo. There was no difference in the age of LEMS onset, gender distribution, incidence of lung cancer, or baseline muscle strength between the patients who were randomly assigned to receive placebo and those randomly assigned to DAP. Statistical analysis using the Wilcoxon's rank sum test demonstrated that patients who received DAP had a significantly greater improvement in the QMG score and in the summated amplitude of compound muscle action potentials recorded from three sentinel limb muscles. All but one LEMS patient had significant symptomatic improvement from subsequent open-label DAP. Side effects of DAP were negligible, consisting of perioral and digital paresthesia. Laboratory measurements demonstrated no evidence of toxicity affecting liver, renal, hematologic, endocrinologic, encephalographic, or electrocardiologic function acutely or after 6 months of open-label DAP. CONCLUSIONS: This study corroborates previous studies and many years of clinical experience showing that DAP is an effective and safe treatment for LEMS.

Significance of blood stream infection after lung transplantation: analysis in 176 consecutive patients.

BACKGROUND: Although infection is a leading cause of death after lung transplantation, very little is known about the incidence, epidemiology, and clinical significance of bloodstream infections in lung transplant recipients. METHODS: All blood cultures were reviewed in 176 consecutive lung transplant recipients over a 6-year period. Data were obtained from a prospectively collected microbiological database. RESULTS: Bloodstream infection (BSI) occurred in 25% (44/176) of all lung transplant recipients over the 6-year study period. Staphylococcus aureus, Pseudomonas aeruginosa, and Candida species were the most common bloodstream isolates after lung transplantation. The epidemiology of posttransplant BSI, however, varied considerably between early and late posttransplant time periods and also differed between cystic fibrosis (CF) and non-CF patients. BSI infection after transplantation was associated with significantly worse survival by Kaplan-Meir analysis (P value log rank test=0.0001). In a multivariable logistic regression model, posttransplant BSI was a significant predictor of posttransplant death (odds ratio 5.62, CI 2.41-13.11, P=0.001), independent of other pre- and posttransplant factors. CONCLUSIONS: Bloodstream infection represents a serious complication after lung transplantation, occurring more frequently than previously recognized, and independently contributing to posttransplant mortality.

Spontaneous diabetes mellitus in the New Zealand white rabbit: physiologic characteristics.

Spontaneous diabetes mellitus has been observed in a female New Zealand white rabbit. By inbreeding of this individual and her offspring, 39 litters comprising 157 animals have been studied and a closed colony of diabetic rabbits established. Three groups of animals can be identified. Twenty-nine (19%) have overt diabetes characterized by fasting hyperglycemia and depressed intravenous glucose stimulated serum insulin levels. This abnormality is seen between 1 and 3 yr of life. Forty-three of the animals (27%) have developed abnormal glucose disposal with normal or slight elevations in fasting serum glucose levels. Glucose stimulated insulin levels are also significantly lower in the rabbits with abnormal glucose disposal. The remaining 85 animals (54%) exhibit no apparent abnormalities of glucose metabolism. All animals with overt diabetes pass through a stage in which glucose disposal as measured by k values is less than 1.0, a value not observed in normal animals. Fasting and arginine stimulated glucagon levels were no different in 4 diabetic animals and 7 normal colony rabbits. Insulin therapy corrected the hyperglycemia in the diabetic rabbits. Insulin was withheld in 5 diabetic rabbits and serum and urinary glucose and ketones were measured for 9 days. Despite marked increases in serum and urinary glucose, only mild ketonemia was observed. The relatively late onset of diabetic symptoms, lack of obesity, severe hyperglycemia, and depressed insulin secretion without ketoacidosis make this a model with many of the characteristics of insulin responsive diabetes as seen in nonobese human adults.

Protease inhibitors are associated with a slowed progression of HIV-related renal diseases.

AIMS: While angiotensin-con-verting enzyme inhibitors and zidovudine may improve the course of the most common HIV-related renal disease, HIV-associated nephropathy (HIVAN), the effect of anti-retroviral combination therapy on this and other HIV-related renal diseases has not been assessed. This study describes the clinical course of HIV-related renal diseases and the effect of protease inhibitors on their progression. METHODS: This retrospective cohort study reviews the clinical course of 19 patients with a clinical or biopsy-proven diagnosis of HIVAN or other HIV-related renal diseases. Groups progressing and not progressing to ESRD were compared using longitudinal analyses to assess the association between creatinine clearance and clinical and therapeutic factors. RESULTS: The cohort consisted of 16 African-Americans, 2 Caucasians and 1 Native American. Their modes of HIV infection were intravenous drug use (7), a history of men having sex with men (3) and heterosexual behavior (5). Patients were followed for a median of 16.6 months. Seven patients reached ESRD. Loss of creatinine clearance over time did not differ among genders, races, or patients with different modes of HIV infection. Longitudinal analyses demonstrated an association between protease inhibitors and prednisone and a slower decline in creatinine clearance in multivariable models (p = 0.04 and 0.003, respectively). CONCLUSIONS: The epidemiology and clinical course of HIV-related renal diseases is more heterogeneous than previously described. This study suggests a benefit to the use of protease inhibitors and prednisone on the progression of these nephropathies.

Prospective assessment of quality of life in ovarian cancer patients receiving whole abdomen hyperthermia and liposomal doxorubicin.

PURPOSE: Prospective assessment of quality of life (QoL) in patients with refractory, residual or recurrent ovarian cancer receiving whole abdomen hyperthermia and intravenous liposomal doxorubicin chemotherapy. METHODS: Treatment consisted of six cycles of intravenous liposomal doxorubicin at 40 mg m2 followed by whole abdomen hyperthermia with each cycle delivered every 4 weeks. QoL assessment was performed at baseline, prior to each cycle of chemotherapy and every 3 months during follow-up using self-administered questionnaires. Global QoL was rated on a seven-point scale and specific domains of QoL, disease related symptoms and treatment related toxicity were rated on a four-point scale. RESULTS: Thirty-two patients were enrolled on the study and 129 QoL questionnaires were completed. Average age was 57.9 (range 45-76); nine patients had persistent and 23 recurrent disease. Ten patients completed six cycles of therapy. Three patients returned follow-up surveys. Subjects rated their overall QoL and health at baseline as above average with mean scores 5.10 (95% CI=4.62-5.58) and 4.66 (95% CI=4.23-5.08), respectively. No significant change in overall QoL was found between baseline and cycles 4-6 of therapy. Mean ratings of overall health and subject reported differences in QoL between cycles were not significantly changed during therapy. Limited follow-up data were available, but scores suggest possible improvement in QoL for patients completing all therapy. Subjects rated the greatest negative impact on QoL in areas of role functioning and social functioning, where the mean (SD) over all cycles was 2.00 (0.67) and 1.98 (0.70), respectively. For physical symptoms, fatigue and sleep disturbance had the most negative impact on QoL with means (SD) of 2.26 (0.62) and 1.91 (0.70). The moderate treatment related toxicity seen in this study did not significantly impact patients reported QoL. CONCLUSIONS: Patients with unfavourable ovarian cancer responding to intravenous liposomal doxorubicin and whole abdomen hyperthermia maintained above average QoL during therapy. Limited data on patients completing protocol therapy demonstrated possible improvement in QoL.

False elevation of hemoglobin A1 by hereditary persistence of fetal hemoglobin.

Measurement of glycosylated hemoglobin (HgA1) is frequently helpful in the management of patients with diabetes mellitus as it provides an index of average glucose control over the previous two to three months. The present case of a diabetic patient with a markedly increased hemoglobin A1 to 42% (normal 5.2-9.2%) with good glucose control prompted an investigation into the etiology of the increased hemoglobin A1 levels. Hemoglobin electrophoresis revealed that the patient had hereditary persistence of fetal hemoglobin. Hemoglobin F was quantitated and found to be responsible for 73% of the hemoglobin A1 determination. Hemoglobin F co-migrates with hemoglobin A1 on column chromatography and, when present in increased quantities, can falsely elevate the measured hemoglobin A1. Thus, if one utilizes the hemoglobin A1 assay to help guide management of patients with diabetes mellitus, it is important to remember that hemoglobin F can cause falsely elevated hemoglobin A1 levels.

Asbestos content of lung tissue and carcinoma of the lung: a clinicopathologic correlation and mineral fiber analysis of 234 cases.

The aim of this study was to investigate the asbestos content of lung tissue in a series of patients with lung cancer and some history of asbestos exposure. This information was then correlated with demographic information, occupational and smoking history, presence or absence of pathologic asbestosis or pleural plaques, and pathologic features of the cancer. The pulmonary concentration of asbestos fibers in 234 cases of primary carcinoma of the lung was determined by means of a tissue digestion technique. Asbestos body counts were performed in 229 cases and fiber analysis by scanning electron microscopy in 221 cases. Asbestos content was recorded as total asbestos fibers, commercial amphibole fibers, noncommercial amphibole fibers, and chrysotile fibers 5 microm or greater in length per gram of wet lung tissue. The study group included 70 patients with asbestosis (Group I), 44 patients with parietal pleural plaques but without asbestosis (Group II), and 120 patients with neither (Group III). The median asbestos body content of Group I was more than 35 times greater than Group II and more than 300 times greater than Group III. The total asbestos fiber count for Group I was nearly 20 times greater than Group II and more than 50 times greater than Group III. The difference was due almost entirely to commercial amphiboles. In a series of primary lung cancer cases with some history of asbestos exposure, a markedly elevated asbestos content was identified among those with pathologic asbestosis as compared with patients with pleural plaques alone or with neither plaques nor asbestosis.

Gastric emptying of hypertonic glucose in diabetes mellitus and duodenal ulcer.

Gastric emptying of hypertonic glucose liquid meals was studied in diabetes, duodenal ulcer, and hospitalized controls by means of the 10% glucose 30-minute test meal, with phenol red as nonabsorbable marker. Acid secreted into the meal was measured. Results revealed no significant difference in gastric emptying between controls and patients with duodenal ulcer and diabetes mellitus. Among diabetics, some individuals empty this meal more rapidly than normal. The results show that alterations of gastric emptying cannot account for the late peaks observed on oral glucose tolerance tests in diabetics, nor for any tendency toward reactive hypoglycemia in duodenal ulcer. They suggest that autovagotomy may occur in some diabetics.

Chlamydia trachomatis infections in the United States. What are they costing us?

Chlamydia trachomatis has emerged as the most common sexually transmitted bacterial pathogen in the United States and is now recognized to cause substantial morbidity. To determine the economic consequences of chlamydial infections in the United States, we analyzed data from local, state, and national sources. We estimate that C trachomatis infections cost Americans over $1.4 billion per year in direct and indirect costs. Chlamydial infections in women account for 79% of this cost, although men and infants are also affected. Three fourths of the total cost is due to sequelae of untreated, uncomplicated infections. If the current rate of chlamydial infection persists, the projected annual costs will exceed $2.18 billion by 1990. Reducing the incidence of personal suffering and heavy economic burden imposed by C trachomatis infections requires establishment and maintenance of effective prevention/control programs.

Treatment of sexually transmitted chlamydial infections.

Tetracycline hydrochloride, 500 mg orally four times a day for seven days, remains the treatment of choice for C trachomatis infections in men and nonpregnant women. Either erythromycin, 500 mg orally four times daily for seven days, or an equivalent dosage of another erythromycin product is an alternative treatment for patients who cannot tolerate tetracycline and for pregnant women. These two treatment regimens can be generalized to include nongonococcal urethritis and mucopurulent cervicitis. However, other treatment regimens that are effective against C trachomatis may not be effective for treating nongonococcal urethritis or mucopurulent cervicitis not caused by C trachomatis. The optimal treatment for pregnant women with C trachomatis infections and women with acute PID has not been established. Additional treatment trials with both groups of patients are needed to determine the effectiveness of antimicrobial agents in addition to those currently used, to establish the appropriate dose of each antimicrobial agent, and to clarify the appropriate duration of treatment. All individuals who are sexual partners of patients with nongonococcal urethritis, mucopurulent cervicitis, and acute PID (within the 30 days prior to onset of their symptoms or time of positive clinical evaluation findings) should be examined for sexually transmitted disease and treated promptly with a regimen effective against uncomplicated gonorrhea and chlamydial infections. Prompt treatment of sexual partners reduces the rate of treatment failure due to reinfection, reduces the transmission of infection, and reduces the frequency of occurrence of adverse sequelae of infection.